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CONCEPTS IN
METABOLISM
• Overview: The Energy of Life
• The living cell
– Is a miniature factory where thousands of
reactions occur
– Converts energy in many ways
• Some organisms
– Convert energy to light, as in bioluminescence
An organism’s metabolism transforms matter
and energy, subject to the laws of
thermodynamics
• Metabolism
– Is the totality of an organism’s chemical
reactions
– Arises from interactions between molecules
Organization of the Chemistry of Life into
Metabolic Pathways
• A metabolic pathway has many steps
– That begin with a specific molecule and end
with a product
– That are each catalyzed by a specific enzyme
Enzyme 1
A
Enzyme 3
D
C
B
Reaction 1
Starting
molecule
Enzyme 2
Reaction 2
Reaction 3
Product
• Catabolic pathways
– Break down complex molecules into simpler
compounds
– Release energy
• Anabolic pathways
– Build complicated molecules from simpler ones
– Consume energy
Exergonic and Endergonic Reactions in Metabolism
• An exergonic reaction
– Proceeds with a net release of free energy and
is spontaneous
Free energy
Reactants
Amount of
energy
released
(∆G <0)
Energy
Products
Progress of the reaction
(a) Exergonic reaction: energy released
• An endergonic reaction
– Is one that absorbs free energy from its
surroundings and is nonspontaneous
Free energy
Products
Amount of
energy
released
(∆G>0)
Energy
Reactants
Progress of the reaction
(b) Endergonic reaction: energy required
Equilibrium and Metabolism
• Reactions in a closed system
– Eventually reach equilibrium
∆G < 0
∆G = 0
(a) A closed hydroelectric system. Water flowing downhill turns a turbine
that drives a generator providing electricity to a light bulb, but only until
the system reaches equilibrium.
• Cells in our body
– Experience a constant flow of materials in and
out, preventing metabolic pathways from
reaching equilibrium
∆G < 0
(b) An open hydroelectric
system. Flowing water
keeps driving the generator
because intake and outflow
of water keep the system
from reaching equlibrium.
• An analogy for cellular respiration
∆G < 0
∆G < 0
∆G < 0
(c) A multistep open hydroelectric system. Cellular respiration is
analogous to this system: Glucose is broken down in a series
of exergonic reactions that power the work of the cell. The product
of each reaction becomes the reactant for the next, so no reaction
reaches equilibrium.
ATP powers cellular work by coupling
exergonic reactions to endergonic
reactions
The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate)
– Is the cell’s energy shuttle
– Provides energy for cellular functions
Adenine
NH2
N
O
O
-O
O
-
O
O
O
-
O
N
CH2
CH
C
N
O
H
Phosphate groups
N
HC
O
O
C
C
H
H
H
OH
OH
Ribose
• Energy is released from ATP
– When the terminal phosphate bond is broken
P
P
P
Adenosine triphosphate (ATP)
H2O
P
i
+
Inorganic phosphate
P
P
Adenosine diphosphate (ADP)
Energy
How ATP Performs Work
• ATP drives endergonic reactions
– By phosphorylation, transferring a phosphate
to other molecules
• The three types of cellular work
– Are powered by the hydrolysis of ATP
P
i
P
Motor protein
Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
ATP
P
P
Solute
P
i
Solute transported
(b) Transport work: ATP phosphorylates transport proteins
P
Glu +
NH2
NH3
Reactants: Glutamic acid
and ammonia
Glu
+
P
i
Product (glutamine)
made
(c) Chemical work: ATP phosphorylates key reactants
i
The Regeneration of ATP
• Catabolic pathways
– Drive the regeneration of ATP from ADP and
phosphate
ATP hydrolysis to
ADP + P i yields energy
ATP synthesis from
ADP + P i requires energy
ATP
Energy from catabolism
(exergonic, energy yielding
processes)
Energy for cellular work
(endergonic, energyconsuming processes)
ADP + P
i
METABOLISM AND ITS
REGULATION
• Metabolic regulation ultimately depends on control
of enzyme activity
• Cells possesses different means of regulating
various metabolic reactions
• A metabolic pathway may have more than one
method of control to ensure that fine regulation
of reaction/s are made to respond to the whole
organism’s needs at any moment
• A catalyst
– Is a chemical agent that speeds up a reaction
without being consumed by the reaction
• An enzyme
– Is a catalytic protein
The Activation Barrier
• Every chemical reaction between molecules
– Involves both bond breaking and bond forming
• The hydrolysis Is an example of a chemical reaction
CH2OH
CH2OH
O
O
H H
H
H
OH
H HO
O
+
CH2OH
H
OH
OH H
Sucrase
H2O
CH2OH
O H
H
H
OH H
OH
HO
H
OH
CH2OH
O
HO
H HO
H
CH2OH
OH H
Sucrose
Glucose
Fructose
C12H22O11
C6H12O6
C6H12O6
• The energy profile for an exergonic reaction
A
B
C
D
Free energy
Transition state
EA
A
B
C
D
Reactants
A
B
∆G < O
C
D
Products
Progress of the reaction
How Enzymes Lower the EA Barrier
• An enzyme catalyzes reactions
– By lowering the EA barrier
• The effect of enzymes on reaction rate
Free energy
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
∆G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
Substrate Specificity of Enzymes
• The substrate
– Is the reactant an enzyme acts on
• The enzyme
– Binds to its substrate, forming an enzymesubstrate complex
• The active site
– Is the region on the enzyme where the
substrate binds
Substate
Active site
Enzyme
(a)
• Induced fit of a substrate
– Brings chemical groups of the active site into
positions that enhance their ability to catalyze
the chemical reaction
Enzyme- substrate
complex
(b)
Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction
– The substrate binds to the active site
1 Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates
Enzyme-substrate
complex
6 Active site
Is available for
two new substrate
Mole.
Enzyme
5 Products are
Released.
Products
2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
3 Active site (and R groups of
its amino acids) can lower EA
and speed up a reaction by
• acting as a template for
substrate orientation,
• stressing the substrates
and stabilizing the
transition state,
• providing a favorable
microenvironment,
• participating directly in the
catalytic reaction.
4 Substrates are
Converted into
Products.
• The active site can lower an EA barrier by
– Orienting substrates correctly
– Straining substrate bonds
– Providing a favorable microenvironment
– Covalently bonding to the substrate
Effects of Local Conditions on Enzyme Activity
• The activity of an enzyme
– Is affected by general environmental factors
Effects of Temperature and pH
• Each enzyme
– Has an optimal temperature in which it can
function
Optimal temperature for
typical human enzyme
Optimal temperature for
enzyme of thermophilic
Rate of reaction
(heat-tolerant)
bacteria
0
20
40
Temperature (Cº)
(a) Optimal temperature for two enzymes
80
100
– Has an optimal pH in which it can function
Optimal pH for pepsin
(stomach enzyme)
Rate of reaction
Optimal pH
for trypsin
(intestinal
enzyme)
3
4
2
1
(b) Optimal pH for two enzymes
0
5
6
7
8
9
Cofactors
• Cofactors
– Are nonprotein enzyme helpers
• Coenzymes
– Are organic cofactors
– NAD+ = Nicotinamide adenine nucleotide
– NADP+ = Nicotinamide adenine dinucleotide
phosphate
– FAD = Flavin adenine dinucleotide
Enzyme Inhibitors
• Competitive inhibitors
– Bind to the active site of an enzyme, competing with
the substrate
A substrate can
bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
(a) Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
(b) Competitive inhibition
Competitive
inhibitor
• Noncompetitive inhibitors
– Bind to another part of an enzyme, changing
the function
A noncompetitive
inhibitor binds to the
enzyme away from
the active site, altering
the conformation of
the enzyme so that its
active site no longer
functions.
Noncompetitive inhibitor
Noncompetitive inhibition
Specific Localization of Enzymes Within the Cell
• Within the cell, enzymes may be
– Grouped into complexes; Incorporated into membranes
Mitochondria,
sites of cellular respiraion
Figure 8.22
1 µm
Photosynthesis vs. Respiration
Photosynthesis
Respiration
1. CO2 and H2O are used
2. Food (CHO) and O2 are produced
3. Energy from light is trapped in
chlorophyll and food
4. ATP is produced by use of light
energy (photosynthetic
phosphorylation)
5. Hydrogen is transferred from H2O to
NADP to form NADPH
6. ATP and NADPH are used primarily
to drive reactions involving sugar
synthesis
7. Carried out in chlorophyll-containing
cells
8. Occurs only in light
9. Occurs in chloroplasts
10. Total photosynthesis must exceed
total respiration for growth to occur
1. O2 and food are used
2. CO2 and H2O are produced
3. Energy in food may be temporarily
store in ATP or lost as heat
4. ATP is produced by oxidation of food
(oxidative phosphorylation)
5. Hydrogen is transferred from food to
NAD or NADP to form NADH or
NADPH
6. ATP and NADH or NADPH are
available to do many types of work
in the cell
7. Occurs in living cells
8. Occurs both in light and darkness
9. Glycolysis occurs in the cytoplasm
while the final steps of aerobic
respiration occur in mitochondria
Plant Energetics Pathway
1. Light Reactions (Hill reactions)
2. Dark Reactions (Calvin Benson)
3. Photorespiration
4. The C4 Pathway (Hatch Slack Pathway)
5. Crassulacean Acid Metabolism (CAM)
Cellular Respiration
1. Glycolysis
2. Anaerobic Respiration
3. Krebb’s Cycle
4. Electron Transport System